1. Field of the Invention
The present invention relates generally to molecular biology and biochemistry and more specifically to a coactivator protein, p/CIP, which is involved in regulating gene expression by CBP/p300-dependent transcription factors, and to methods of using the coactivator protein to selectively regulate gene expression.
2. Background Information
Regulation of gene expression is mediated by sequence-specific transcription factors that bind to target genes and activate or repress transcription. Many of these factors are controlled by extracellular signals that switch the factors between inactive and active states. Such signals can result in post-translational modification as observed, for example, with the members of the STAT family of transcription factors, or can result in ligand-induced conformational changes as observed, for example, with members of the nuclear receptor family of transcription factors.
Coactivator proteins have been identified that are recruited to the active forms of such transcription factors and are required for their transcriptional effects. The coactivators, CBP and p300, for example, serve essential roles in transcriptional activation by several classes of regulated transcription factors, including nuclear receptors, STAT factors, AP-1 proteins, NF-κB and CREB. In addition, a more recently discovered family of proteins, termed nuclear receptor coactivator (NCoA) proteins, can interact with various nuclear receptors in a ligand-dependent manner and also can interact with CBP and p300.
Two members of the NCoA family of proteins, NCoA-1 and NCoA-2, appear to have relatively selective roles in mediating the transcriptional effects of nuclear receptors. Evidence indicates, however, that additional factors are required for the transcriptional activities of many CBP-dependent transcription factors, including STAT 1, AP-1 and CREB, and that complexes containing such coactivators, for example, CBP/p300 and NCoA, are involved in transmitting an activation signal to the promoter. Since CBP and p300-containing complexes appear to be limiting in cells, antagonistic interactions between signaling pathways can be due, at least in part, to competition for these complexes. Thus, a need exists to identify different classes of transcription factors that are regulated by a CBP-containing complex and to identify the coactivator proteins involved in such complexes. The present invention satisfies this need and provides related advantages as well.